The present study aimed to predict a novel chimeric vaccine by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and normal mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data.

SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis.Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level.In addition, disulfide engineering was investigated to accelerate the stability of the protein.Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study.However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.

No abstract

Candida auris is a serious health concern of current world that possess serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistance toward those drugs and some strains have already showed resistant to all three available antifungal drugs in the market. Finding alternative treatments is a must, therefore, to save lives from this foe. To make the way easier for developing new treatments, we have made some insilico analysis of this pathogen to identify suitable targets for designing drugs and also suggested some potential metabolites to test in vivo condition after some computational analysis. After the subtraction of duplicate, non-essential, human homologs, non-metabolic, human microbiome similar and druggable proteins we ended up with three proteins (XP_028890156.1, XP_028891672.1 and XP_028891858.1) from a total of 5441 C. auris proteins. Blocking those proteins will result in the destruction of the pathogen while the host will remain safe from unintentional blocking. Their subcellular locations and interaction with high number of proteins also indicate their suitability as drug target candidates. After analyzing in silico docking of 29 potential antifungal from plant origin with those three proteins we selected Caledonixanthone E, Viniferin, Glaucine, Jatrorrhizine as the most potent weapon to block those proteins as they showed higher binding affinity. Furthermore, they were predicted to be safe and also showed proper ADME properties (Figure 1).

No abstract